Triethylamine → 2-[1-(2-Chloro-9,10-dihydro-9,10-methanoanthracen-9-ylmethyl)-4-piperidylamino]pyrimidine

HRID 2209602Notes

Reaction equation

HRID 2209602 reaction equation
[NH2:1][CH:2]1[CH2:7][CH2:6][N:5]([CH2:8][C:9]23[CH2:24][CH:16]([C:17]4[CH:18]=[CH:19][C:20]([Cl:23])=[CH:21][C:22]=42)[C:15]2[C:10]3=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH2:4][CH2:3]1.Cl[C:26]1[N:31]=[CH:30][CH:29]=[CH:28][N:27]=1.C(N(CC)CC)C>CN1CCCC1=O>[Cl:23][C:20]1[CH:19]=[CH:18][C:17]2[CH:16]3[CH2:24][C:9]([CH2:8][N:5]4[CH2:6][CH2:7][CH:2]([NH:1][C:26]5[N:31]=[CH:30][CH:29]=[CH:28][N:27]=5)[CH2:3][CH2:4]4)([C:10]4[C:15]3=[CH:14][CH:13]=[CH:12][CH:11]=4)[C:22]=2[CH:21]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 744042-ChloropyrimidineHCID 193809734-Amino-1-(2-chloro-9,10-dihydro-9,10-methanoanthracen-9-ylmethyl)piperidine

Product 1

HCID 193810102-[1-(2-Chloro-9,10-dihydro-9,10-methanoanthracen-9-ylmethyl)-4-piperidylamino]pyrimidine

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

4-amino-1-(2-chloro-9,10-dihydro-9,10-methanoanthracen-9-ylmethyl)piperidine (0.500 g, 1.48 mmol, prepared as described in Example 7b) was heated to 100° C. for 5 hours in 1.5 mL N-methylpyrrolidinone with 2-chloropyrimidine (0.212 g, 1.85 mmol, commercial grade purified by extraction into petroleum ether) and triethylamine (0.300 g, 29.6 mmol) under a nitrogen atmosphere. Aqueous method (3 mL, 50% v/v) was added to the warm (50° C.) reaction mixture to give a white precipitate. The solid was collected by filtration and washed with fresh aqueous methanol (5 mL, 50% v/v) to give the title compound as a white solid. The solid was dissolved in methanolic hydrogen chloride, evaporated to dryness on a rotary evaporator, redissolved in a minimum volume of fresh methanol (2 mL) and added at a slow dropwise rate to rapidly stirring ethyl ether (80 mL) to precipitate the hydrochloride salt as a white solid (0.414 g, 0.99 mmol, 67%), mp 212°-214° C.; MS(CI) 417 (M+H); NMR (250 MHz, DMSO-d6): 10.17(br s, 1H), 8.38-8.33(m, 2H), 7.67(br m, 1H), 7.52-7.49(m, 1H, 7.38-7.31(m, 3H), 7.05-6.96(m, 3H), 6.70-6.63(m, 1H), 4.47(s, 1H), 4.35-4.29(m, 2H), 4.16(br m, 1H), 3.57-3.36(m, 4H), 2.76(m, 2H), 2.12-1.90 (m, 4H).

Workup

  1. additionAqueous method (3 mL, 50% v/v) was added to the
  2. temperaturewarm
  3. custom(50° C.) reaction mixture
  4. customto give a white precipitate
  5. filtrationThe solid was collected by filtration
  6. washwashed with fresh aqueous methanol (5 mL, 50% v/v)

Sources & evidence

ORD record
ord-96e2b809c9d148c49f25ccf0adde907b
Source dataset
uspto-grants-1995_10
Patent number
US05455246

Reaction notes

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